We have extensive data already collected on 68 multiple-case families in which the index case has premenopausal bilateral breast cancer. These data include DNA, family history, and exposure to breast cancer risk factors for most family members and, on cases, pathology reports and paraffin blocks of tumor tissue. We are currently conducting numerous analyses including linkage analyses of markers and candidate genes on l7q and gene-environment interactions. What we propose here is to determine losses of heterozygosity for the cases in our families. We will use recently developed techniques to extract DNA from the paraffin blocks and PCR-based techniques to determine markers for constitutional vs tumor DNA. Chromosome regions of particular interest include 1P, 3p, 13, l7q, 17p. Specific candidate genes of interest include AT, RB, P53, and candidate genes in the 1P and l7q regions. We propose to 1) estimate the prevalence of LOH's in the largest series to date of early onset bilateral breast cancer, 2) compare LOH's in the right vs left breasts of bilateral cases, 3) compare LOH's between cases within a family since we have multiple-case families, and 4) investigate environmental effects on LOH's, i.e. LOH- environment interactions. We will conduct these analyses within subgroups of families that are positive and negative for linkage to 17q, and other linkages as they are found. The results will help us deal with the issue of heterogeneity that plagues breast cancer work and will elucidate genetic events, both somatic and inherited, and gene-environment interactions that are involved in the etiology of breast cancer.